There is an almost uniform occurrence of peripheral neuropathy in patients with longstanding diabetes mellitus. Recently, we found that there is thickening of the basement membranes of the perineurial cell, Schwann cell, and capillary endotheilal cell in diabetic peripheral nerves. These basement membrane changes and the accompanying peripheral neuropathy have not been studied in a correlative prospective manner in terms of their clinical, structural, and biochemical features. The overall aim of the proposed project is to perform such a study. Samples of peripheral nerve from multiple sites and skeletal muscle will be obtained from diabetic and nondiabetic patients coming to autopsy. Quantitative morphologic study of the nerves and muscle will evaluate basement membrane changes and disease states (i.e., peripheral neuropathy). Basement membrane will be isolated from these nerves by a newly devised method and will be analyzed biochemically. Patient data will be collected (i.e., duration of diabetes, type of therapy, age, etc.) for correlation with the anatomical and biochemical data. Examples of questions to be addressed are the following: 1. Are there differences in the amino acid, and carbohydrate, composition of peripheral nerve basement membranes derived from normal and diabetic human subjects? 2. Do the biochemical and morphological abnormalities observed correlate with the severity of diabetes or with accompanying conditions such as advanced age? 3. Are there qualitative and/or quantitative changes in glycoprotein and collagenous components of periphera nerve basement membranes in diabetes? 4. Is the crosslinking of the basement membrane altered in peripheral nerve from diabetic subjects? 5. Is there a correlation between the degree and nature of the neuropathy and structure-composition changes in basement membrane? 6. Do the basement membranes of nerve thicken in parellel with skeletal muscle?